PSENEN Mutation Carriers with Co-manifestation of Acne Inversa (AI) and Dowling-Degos Disease (DDD): Is AI or DDD the Subphenotype?

Li, Chengrang; Li, Wenrui; Xu, Haoxiang; Zhang, Xiaofeng; Su, Binbin; Zhang, Wanlu; Zhang, Xue; Wang, Baoxi

doi:10.1016/j.jid.2017.05.021

Cited by 21 publications

(22 citation statements)

References 12 publications

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“…Reticulate hyperpigmentation similar to that observed in Dowling–Degos disease has also been reported together with HS in patients with PSENEN mutations (MIM 613736) . Additional gene defects in the Notch signalling pathway could also be important for HS and Dowling–Degos disease, such as the recently reported mutations in POFUT1 and POGLUT1 …”

Section: Human Disorders That Cause Acne‐like Phenotypesmentioning

confidence: 63%

“…[102][103][104] Additional gene defects in the Notch signalling pathway could also be important for HS and Dowling-Degos disease, such as the recently reported mutations in POFUT1 and POGLUT1. [105][106][107][108][109] Mutations in genes from the c-secretase complex result in haploinsufficiency, which is predicted to decrease activity of Notch signalling in the skin. 101 c-Secretase is an enzyme complex of four proteins that cleaves the intracellular domain of Notch, allowing translocation to the nucleus and activation of Notch target genes.…”

Section: Hidradenitis Suppurativa (Mim 142690)mentioning

confidence: 99%

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What does acne genetics teach us about disease pathogenesis?

2019

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Summary Background Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking. Results The advent of high‐resolution genotyping array technologies has allowed for large‐scale studies with both family‐based and cross‐sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne‐like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris. Conclusions The next phase of research will require more in‐depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets.

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Section: Human Disorders That Cause Acne‐like Phenotypesmentioning

confidence: 63%

Section: Hidradenitis Suppurativa (Mim 142690)mentioning

confidence: 99%

What does acne genetics teach us about disease pathogenesis?

2019

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“…Interestingly mutations in PSENEN results in 3 different phenotypes: (1) HS, (2) Dowling-Degos Disease (DDD), or (3) HS and DDD (47, 49), whilst DDD is not associated with any mutations in NCSTN .…”

Section: Genomicsmentioning

confidence: 99%

An Integrated Approach to Unravel Hidradenitis Suppurativa Etiopathogenesis

et al. 2019

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Hidradenitis suppurativa/acne inversa (HS) is a chronic inflammatory disease involving hair follicles that presents with painful nodules, abscesses, fistulae, and hypertrophic scars, typically occurring in apocrine gland bearing skin. Establishing a diagnosis of HS may take up to 7 years after disease onset. HS severely impairs the quality of life of patients and its high frequency causes significant costs for health care system. HS patients have an increased risk of developing associated diseases, such as inflammatory bowel diseases and spondyloarthropathies, thereby suggesting a common pathophysiological mechanism. Familial cases, which are around 35% of HS patients, have allowed the identification of susceptibility genes. HS is perceived as a complex disease where environmental factors trigger chronic inflammation in the skin of genetically predisposed individuals. Despite the efforts made to understand HS etiopathogenesis, the exact mechanisms at the basis of the disease need to be still unraveled. In this review, we considered all OMICs studies performed on HS and observed that OMICs contribution in the context of HS appeared as not clear enough and/or rich of useful clinical information. Indeed, most studies focused only on one aspect—genome, transcriptome, or proteome—of the disease, enrolling small numbers of patients. This is quite limiting for the genetic studies, from different geographical areas and looking at a few aspects of HS pathogenesis without any integration of the findings obtained or a comparison among different studies. A strong need for an integrated approach using OMICs tools is required to discover novel actors involved in HS etiopathogenesis. Moreover, we suggest the constitution of consortia to enroll a higher number of patients to be analyzed following common and consensus OMICs strategies. Comparison and integration with the findings present in the OMICs repositories are mandatory. In a theoretic pipeline, the Skin-OMICs profile obtained from each HS patient should be compared and integrated with repositories and literature data by using appropriate InterOMICs approach. The final goal is not only to improve the knowledge of HS etiopathogenesis but also to provide novel tools to the clinicians with the eventual aim of offering a tailored treatment for HS patients.

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“…The clinical and genetic overlap of HS-DDD may also have a clinical relevance, translating into a personalized therapeutic management, such as the combination of retinoids and sulfones. 8 S. Garcovich iD , 1.2 P.M. Tricarico, 3 C. Nait-Meddour, 4,5 G. Giovanardi, 1,2 K. Peris, 1,2 S. Crovella 3,6 and M. Boniotto iD…”

mentioning

confidence: 99%

Novel nicastrin mutation in hidradenitis suppurativa–Dowling–Degos disease clinical phenotype: more than just clinical overlap?

et al. 2020

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DEAR EDITOR, In familial hidradenitis suppurativa (HS), mutations in the genes encoding three subunits of the gamma secretase complex, presenilin-1 (PSEN1), presenilin enhancer (PSENEN) and nicastrin (NCSTN), have pointed to impaired Notch signalling as a pathogenic disease mechanism. 1 Dowling-Degos disease (DDD; MIM 179850, 615327 and 615696), a rare reticulated pigmentary disorder, has also been

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PSENEN Mutation Carriers with Co-manifestation of Acne Inversa (AI) and Dowling-Degos Disease (DDD): Is AI or DDD the Subphenotype?

Abstract: Germline mutation in EXPH5 implicates the Rab27B effector protein Slac2-b in inherited skin fragility. Am J Hum Genet 2012;91:1115e21.

Cited by 21 publications

References 12 publications

What does acne genetics teach us about disease pathogenesis?

What does acne genetics teach us about disease pathogenesis?

An Integrated Approach to Unravel Hidradenitis Suppurativa Etiopathogenesis

Novel nicastrin mutation in hidradenitis suppurativa–Dowling–Degos disease clinical phenotype: more than just clinical overlap?

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